Principal Investigator/Program Director (Last, first, middle): Watkins, Linda RESEARCH &RELATED Other Project Information 1. * Are Human Subjects Involved? m Yes l No 1.a. If YES to Human Subjects Is the IRB review Pending? m Yes m No IRB Approval Date: Exemption Number: 1 2 3 4 5 6 Human Subject Assurance Number 2. * Are Vertebrate Animals Used? l Yes m No 2.a. If YES to Vertebrate Animals Is the IACUC review Pending? l Yes m No IACUC Approval Date: Animal Welfare Assurance Number A3646-01 3. * Is proprietary/privileged information m Yes l No included in the application? 4.a.* Does this project have an actual or potential impact on m Yes l No the environment? 4.b. If yes, please explain: 4.c. If this project has an actual or potential impact on the environment, has an exemption been authorized or an environmental assessment (EA) or environmental impact statement (EIS) been performed? m Yes m No 4.d. If yes, please explain: 5.a.* Does this project involve activities outside the U.S. or m Yes l No partnership with International Collaborators? 5.b. If yes, identify countries: 5.c. Optional Explanation: 6. * Project Summary/Abstract 7854-Watkins.ProjectSummary.pdf Mime Type: application/pdf 7. * Project Narrative 176-Watkins.ProjectNarrative.pdf Mime Type: application/pdf 8. Bibliography &References Cited 1004-Watkins.LiteratureCited.pdf Mime Type: application/pdf 9. Facilities &Other Resources 8902-Watkins.Facilities.pdf Mime Type: application/pdf 10. Equipment 5753-Watkins.Equipment.pdf Mime Type: application/pdf Tracking Number: Other Information Page 5 OMB Number: 4040-0001 Expiration Date: 04/30/2008 Principal Investigator/Program Director (Last, first, middle): Watkins, Linda It has recently been discovered that glia become progressively more activated upon repeated exposure to morphine, &that this glial activation, in turn, modulates morphine's effects. This discovery was originally made in the context of studying the pain suppressive effects of morphine in spinal cord. The possibility that glia may be fundamentally important in determining the effects of opioids such as morphine is novel &important in its implications. Because of this, we propose to explore whether glia may profoundly alter the effects of repeated morphine in brain, as well. We believe that glia will prove to be powerfully involved in several phenomena currently thought to arise purely as a result of opioid effects on neurons;that is, dependence/withdrawal, reward &aversion. If this were true, it would provide evidence that glia are critically involved, not only in modulating the pain-suppressive effects of opioids, but also in